11517 Background: Neoplastic meningitis (NM) is diagnosed in 5–8% of patients with solid tumors. Unknown primary cancers (UPC) constitute 1% to 7% of NM cases. There is scattered data addressing NM in the context of UPC. Here we characterize the clinical manifestations, prognostic factors and survival outcomes in patients with NM from UPC. Methods: Through an IRB-approved, retrospective chart-review, spanning 1944–2002, we identified 38 patients with UPC, with NM either the presenting feature or a later manifestation of their systemic cancer. Imaging studies were also reviewed. Results: Median age at UPC diagnosis was 44 (13–72 years); for those patients not presenting with NM, time from UPC diagnosis to NM diagnosis was 10 weeks (range 3–60 weeks). Five patients presented with NM as the first and only manifestation of cancer, 1 presented with NM simultaneously with UPC, and 32 patients presented with UPC, followed by NM. Sixteen of those 32 patients presented with central nervous system (CNS) metastases concomitantly with their UPC diagnosis. The final cancer diagnoses were: melanoma (n=21), adenocarcinoma (n=12), small cell undifferentiated carcinoma (n=2), undifferentiated malignant tumor (n=1), Ewing sarcoma (n=1) and sarcomatoid carcinoma (n=1). The median overall survival after the initial diagnosis of UPC was 54 weeks (range: 6–344 weeks), and the median survival after the diagnosis of NM was 10.7 weeks (range: 2–132 weeks). Thirteen patients had a prolonged survival after the diagnosis of NM (24–132 weeks), 8 with melanoma, 3 with adenocarcinoma, 2 with small cell cancer. Six of the 8 melanoma patients with prolonged survival presented with only CNS disease, and none developed other metastatic sites during the course of their disease. Conclusions: Patients with NM and UPC have a poor prognosis. The most commonly identified primary tumors in patients with NM and UPC are melanoma and adenocarcinoma. UPC presenting as NM, and found to be melanoma limited to the CNS and or meninges, carries a better prognosis than other UPCs with NM where systemic tumor burden is identified. This may aid in the systemic diagnostic evaluation and treatment of such patients. No significant financial relationships to disclose.